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# Norepinephrine
## Overview
Norepinephrine is a vasopressor and inotropic agent that acts on alpha- and beta-adrenergic receptors. It increases systemic vascular resistance and blood pressure, and to a lesser extent, myocardial contractility.
## Primary Indications
* Treatment of hypotension and shock (e.g., septic shock, cardiogenic shock, hypovolemic shock) unresponsive to adequate fluid resuscitation.
## Adult Dosing
* **Initial Infusion Rate:** Typically initiated at 0.01 to 0.05 mcg/kg/minute.
* **Titration:** Gradually increased by 0.01 to 0.05 mcg/kg/minute increments every 5 to 10 minutes as needed to achieve target blood pressure.
* **Maximum Dose:** Doses up to 1 to 3 mcg/kg/minute may be required in severe cases, but doses exceeding 0.5 mcg/kg/minute are associated with increased risk of adverse effects. Optimal dose is patient-specific and guided by response.
## Pediatric Dosing
* **Initial Infusion Rate:** Typically initiated at 0.05 to 0.1 mcg/kg/minute.
* **Titration:** May be increased to 0.1 to 2 mcg/kg/minute based on patient response.
* **Maximum Dose:** Doses up to 2 mcg/kg/minute or higher may be necessary in refractory shock, but higher doses increase the risk of adverse events. Exact dosing often determined by local protocol and expert consultation.
## Dose Adjustments
* **Renal Impairment:** No specific dose adjustment is generally recommended, but caution is advised due to potential accumulation and prolonged effects.
* **Hepatic Impairment:** No specific dose adjustment is generally recommended, but caution is advised.
## Contraindications
* Hypersensitivity to norepinephrine.
* Use during cyclopropane and halogenated hydrocarbon anesthesia (risk of severe hypertension and arrhythmias).
## Adverse Effects
* **Cardiovascular:** Hypertension, reflex bradycardia, arrhythmias, peripheral ischemia, tissue necrosis (especially with extravasation), angina.
* **Central Nervous System:** Headache, anxiety, dizziness, tremors.
* **Metabolic:** Hyperglycemia.
## Key Drug Interactions
* **Monoamine Oxidase Inhibitors (MAOIs):** Potentiated pressor response, potentially severe hypertension. Avoid concomitant use; if necessary, use extreme caution and reduce norepinephrine dose significantly.
* **Tricyclic Antidepressants (TCAs):** Potentiated pressor response. Use with caution.
* **Beta-blockers:** Can block the beta-mediated cardiac effects of norepinephrine, potentially leading to unopposed alpha-adrenergic vasoconstriction and severe hypertension.
* **Alpha-blockers:** May reduce the pressor effect of norepinephrine.
* **Ergot Alkaloids:** Increased risk of peripheral vasoconstriction and ischemia.
* **Oxytocics:** May cause severe hypertension.
## Monitoring
* **Hemodynamics:** Continuous blood pressure monitoring (arterial line preferred), heart rate, cardiac rhythm.
* **Urine Output:** To assess adequate tissue perfusion.
* **Lactate Levels:** To assess tissue perfusion and response to treatment.
* **Extremities:** Assess for signs of peripheral ischemia (color, temperature, capillary refill).
* **Infusion Site:** Monitor closely for signs of extravasation.
## Clinical Pearls
* Norepinephrine is a potent vasoconstrictor and must be administered via a central venous catheter whenever possible to minimize risk of extravasation and tissue necrosis.
* If extravasation occurs, discontinue the infusion, aspirate any remaining drug, and administer phentolamine mesylate subcutaneously to the affected area.
* Titrate to the lowest effective dose to achieve target blood pressure and perfusion endpoints, not just a specific numerical value.
* Norepinephrine is often the vasopressor of choice in septic shock due to its balanced alpha and beta effects.
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*Disclaimer: This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines before making any treatment decisions.*
